The Levine Laboratory
Edward Levine joined the Moran Eye Center in 2000. His laboratory is focused on understanding the molecular and cellular mechanisms of retinal development, as well as determining the contributions of developmental mechanisms to the progression and treatment of retinal degenerative diseases. His research uses the mouse retina because its developmental progression is well understood and several genetic models of retinal degeneration are available, thus facilitating the identification and characterization of important regulatory molecules. These studies enable direct tests of the roles of these molecules in retinal degenerations.
In the developing vertebrate retina, multipotential progenitor cells respond to environmental signals to expand the progenitor pool and generate one glial and six neuronal cell types. For this to occur, proliferation and differentiation must be balanced. The observation that cell cycle withdrawal precedes the onset of cellular differentiation suggests that the regulation of these processes is tightly linked. To address this, we are identifying the genes expressed in retinal progenitors that regulate the cell cycle and coordinate cell cycle withdrawal with the onset of differentiation.
Education: Ph.D., State University of New York, Stony Brook
Academic Appointments: Assistant Professor of Ophthalmology & Visual Sciences—University of Utah School of Medicine
Patient Care Significance
Once the retina is “built” from progenitor cells, the resulting neurons must survive for the life of the organism. Neurons do not replenish themselves. Many retinal diseases attack the neurons of the retina, leading to severe visual impairment and blindness. Understanding how retinal neurons cells are produced and differentiate may offer us the ability to build retinas anew, design novel synthetic retinas, or replenish populations of photoreceptor cells that have been depleted by retinal degenerations such as retinitis pigmentosa and macular degeneration. The Levine Laboratory has identified key genes that control the proliferation and differentiation of retinal progenitor cells and is studying ways to grow, harvest and use these cells. The Levine Laboratory is the Moran Eye Center’s lead group for basic research on stem and progenitor cells in the retina.
Major publications from the Levine Laboratory
Levine E. M., and Green E. S. (2004) Cell-intrinsic regulation of proliferation in vertebrate retinal progenitors. Seminars in Cell and Developmental Biology, 15:63-74.
Levine E. M. (2004) Cell cycling through development. Development, 131:2241-2246.
Green E. S., Stubbs J. L., and Levine E. M. (2003) Genetic rescue of cell number in a mouse model of microphthalmia: interactions of Chx10 with G1 cell cycle regulators. Development, 130:539-552.
Defoe D. M., and Levine E. M. (2003) Expression of the cyclin-dependent kinase inhibitor p27Kip1 by developing retinal pigment epithelium. Gene Expression Patterns, 3:615-619.
Cunningham J.J., Levine E. M., Zindy F., Roussel M. F., Smeyne R. J. The cyclin-dependent kinase inhibitors, p19Ink4d and p27Kip1, are co-expressed in select retinal cells and act co-operatively to control cell cycle exit. Molecular and Cellular Neuroscience (2002) 19:359-374.
Das, G., Choi, Y., Sicinski, P., Levine, E.M. (2009) Cyclin D1 fine-tunes the neurogenic output of embryonic retinal progenitor cells. BMC Neural Development, 4(1):15
Sigulinsky, C., Green, E.S., Clark, A.M., Levine, E.M. (2008) Vsx2/Chx10 ensures the correct timing and magnitude of Sonic Hedgehog signaling in retinal progenitor cells. Developmental Biology, 317:560-575
Clark, A.M., Yun, S., Veien, E.S., Wu, Y.Y., Chow, R.L., Dorsky, R.I., Levine, E.M. (2008) Negative regulation of Vsx1 by its paralog Chx10 is conserved in the vertebrate retina. Brain Research, 1192:99-113
Dhomen, N.S., Balaggan, K.S., Bainbridge, J.W., Rae, J., Levine, E.M., Ali, R.R., Sowden, J.C. (2006) Absence of Chx10 causes neural progenitors to persist in the adult retina. Investigative Ophthalmology and Visual Sciences, 47:386-396
Levine, E.M., Green, E.S. (2004) Cell-intrinsic regulators of proliferation in vertebrate retinal progenitors. Seminars in Cell and Developmental Biology 15:63-74
Green, E.S., Stubbs, J.L., Levine, E.M. (2003) Genetic rescue of cell number in a mouse model of micropththalmia: interactions between Chx10 and G1 phase cell cycle regulators. Development 130:539-552